Expression and functional role of β-adrenoceptors in the human urinary bladder urothelium

We investigated the presence of beta-adrenoceptor subtypes in human urinary bladder urothelium and examined whether beta-adrenoceptors in the urothelium modulate the relaxation responses of isolated human detrusor strips to a beta-adrenoceptor agonist. Expression of beta(1)-, beta(2)-, and beta(3)-adrenoceptor mRNA in urothelium and detrusor smooth muscle was determined by reverse transcription-polymerase chain reaction, and the distribution of beta(1)-, beta(2)-, and beta(3)-adrenoceptors in human urinary bladder urothelium were examined by immunohistochemistry. Paired human longitudinal detrusor strips with and without an intact urothelium were suspended in organ baths to construct concentration-response curves to isoproterenol. The possible involvement of urothelium-derived nitric oxide (NO) in this response was examined in additional experiments with urothelium-intact strips in the presence of N-G-nitro-L-arginine methylester (L-NAME). Results confirmed the expression of beta(1)-, beta(2)-, and beta(3)-adrenoceptors in the human urinary bladder urothelium. Further, the presence of the urothelium caused a parallel rightward shift of the concentration-response curve to isoproterenol with a significant reduction in potency (pEC(50)). L-NAME failed to exert any significant effect on the relaxation response to isoproterenol in the urothelium-intact strips. These results confirm the presence of beta(1)-, beta(2)-, and beta(3)-adrenoceptors in human urinary bladder urothelium. Further, they suggest that urothelial beta-adrenoceptors induce the release of a urothelium-derived factor which inhibits the beta-adrenoceptor agonist-induced relaxation of the human detrusor smooth muscle and that this inhibitory mechanism might not involve NO.